Non-invasive intracranial pressure detection device and method

Abstract

One aspect of the present disclosure provides a non-invasive intracranial pressure detection device comprising an interferometric near-infrared spectroscopy (iNIRS) system, the iNIRS system comprising a light source configured to emit light, a sample delivery channel coupled to the light source and arranged to be coupled to the subject's scalp for directing light from the light source towards the subject's brain tissue, a reference channel coupled to the light source for receiving light from the light source, an emitting device comprising the reference channel, and a light detection device configured to couple the subject's scalp to the emitting device, the light detection device comprising an interferometric photodetector configured to receive (i) reference light from the reference channel and (ii) sample light from the subject's brain, the sample light including light emitted from the light source, the interferometric photodetector being arranged to couple the sample light and the reference light to provide a combined optical signal including one or more components of the beat frequency between the sample light and the reference light, the light detection device comprising a control device configured to process data indicative of the combined optical signal to determine an indication of the intracranial blood pressure of the subject based on at least one characteristic of the pulsatile waveform of one or more identified pulses of blood flow through the subject's brain.

Description

Technical Field

[0001] The present disclosure relates to the field of neuroimaging and analysis. In particular, the present disclosure relates to an interferometric near-infrared spectroscopy (iNIRS) system and method for performing neuroimaging and analysis.

Background Art

[0002] Near-infrared spectroscopy (NIRS) is a spectroscopic method that uses the near-infrared region of the electromagnetic spectrum (e.g., between 780 nm and 2500 nm). NIRS systems can be used to provide non-invasive monitoring of the scattering and absorption characteristics of a medium. Since radiation at NIRS wavelengths is not as readily absorbed by human skin (and bone) as visible light, NIRS radiation can penetrate the skin and skull and enter the brain tissue. NIRS can be used as a method for non-invasively imaging the human brain tissue by monitoring the scattering and absorption characteristics of NIRS radiation within the brain tissue.

[0003] While the NIRS method can be extended to monitor oxygenation, when multiple wavelengths are used, blood flow monitoring is required to infer information about metabolic activity. Diffuse correlation spectroscopy (DCS) can be used to non-invasively monitor blood flow in the brain by measuring the temporal fluctuations of light sent from a sample. DCS can further extract other brain metrics including intracranial pressure (ICP). However, to extract ICP, existing DCS methods require additional equipment and a large amount of averaging, making the final approach difficult to handle and slow. Also, to quantify blood flow, DCS typically requires optical properties that are either inferred from or obtained from another NIRS device. And since DCS and NIRS rely only on light intensity, they discard half of the information about scattered light encoded in the optical phase. As a result, the measurements are subject to further inference by ignoring the phase information.

[0004] Therefore, it is desirable to provide an improved technique for nerve monitoring and analysis by combining NIRS and DCS as one imaging means, and to rapidly provide the optical properties and dynamic properties of biological tissues.

SUMMARY OF THE INVENTION

[0005] Aspects of the present disclosure are set forth in the independent claims, and optional features are set forth in the dependent claims. Aspects of the present disclosure may be provided in combination, and features of one aspect may be applied to other aspects.

[0006] In one aspect, a non-invasive intracranial pressure detection device comprising an interferometric near-infrared spectroscopy ("iNIRS") system is provided. The iNIRS system includes a light source configured to emit light (e.g., light having a swept wavelength), a sample delivery channel disposed to be coupled to the subject's scalp for directing light from the light source toward the subject's brain tissue, a reference channel coupled to the light source for receiving light from the light source, an emitting device comprising the reference channel, and a light detection device configured to couple the subject's scalp to the emitting device, the light detection device comprising: (i) reference light from the reference channel; and (ii) sample light from the subject's brain tissue, the sample light including light emitted from the light source (e.g., a portion of which may pass through the subject's scalp and skull and through a portion of the brain tissue before scattering toward the detector). An interferometric light detector configured to receive the sample light and the reference light, the interferometric light detector being arranged to combine the sample light and the reference light to provide a combined optical signal including one or more components of the beat frequency between the sample light and the reference light. The light detection device includes a control device configured to process data indicative of the combined optical signal to obtain an indication of the intracranial blood pressure of the subject based on at least one characteristic of the pulsatile waveform of one or more identified pulses of blood flow through the subject's brain tissue.

[0007] An embodiment may non-invasively acquire intracranial blood pressure (hereinafter referred to as "ICP"). This may be advantageous because alternative methods for determining ICP can be very invasive, such that their use may be limited only to situations where ICP measurement is most needed (and thus worth the high risk associated with invasive ICP measurement).

[0008] Processing data indicative of the combined optical signal may include obtaining blood flow data indicative of one or more pulses of blood flow through the subject's brain. For example, the blood flow data may include data including a cerebral blood flow index value. The cerebral blood flow index value may provide an indication of the velocity of the movement of blood in a given volume of the subject's brain. The control device may be configured to obtain extracranial blood flow data indicative of one or more pulses of blood flow through an extracranial region of the subject's body. The extracranial blood flow data may include blood pressure values of one or more pulses of extracranial blood flow. The extracranial blood flow data may include blood flow index values of one or more pulses of extracranial blood flow (and the control device may be configured to determine a corresponding extracranial blood pressure value from this blood flow index value).

[0009] The control device may be configured to determine an indication of the intracranial blood pressure of the subject based on both the cerebral blood flow data and the extracranial blood flow data. The control device may determine an indication of ICP based on a comparison of the cerebral blood flow data and the extracranial blood flow data. Comparing these two data may include aligning the cerebral blood flow data with the extracranial blood flow data such that the pulses of blood through the subject's brain tissue are aligned with the corresponding pulses of blood flow through the extracranial region of the subject's body. Aligning may include associating each intracranial pulse of blood flow with the corresponding extracranial pulse of blood flow (such that, for example, even if the two pulses are slightly out of phase due to being measured in different regions of the subject's body, they correspond to the same cardiac cycle). Comparing the two pulses may include comparing (i) one or more characteristics of the pulsation waveform of the pulse of blood flow through the subject's brain tissue with (ii) one or more characteristics of the pulsation waveform of the pulse of blood flow through the extracranial region of the subject's body.

[0010] The extracranial blood flow data may include an indication of the blood pressure value of the pulse of the blood flow through the extracranial region of the subject's body. For example, the extracranial blood flow may be for a shallow (e.g., not very deep) region of the subject's body, such as the subject's scalp (which is on top of the subject's skull). For example, the extracranial blood flow data may include a series of (e.g., a time-ordered series of) blood pressure values of the subject in the extracranial region of the subject's body. The extracranial blood flow data may provide blood pressure values for the pulsation waveform of each pulse of the blood flow (e.g., indicating the blood pressure values at a plurality of points in each pulse of the blood flow through the extracranial region of the subject's body). The control device may be configured to determine an indication of the intracranial blood pressure of the subject based on (i) the pulsation waveform of one or more specified pulses of the blood flow through the subject's brain tissue and (ii) the corresponding pulsation waveform for the blood pressure of one or more pulses of the blood flow through the extracranial region of the subject's body.

[0011] For example, the control device may be configured to determine the ICP based on the extracranial blood pressure value at a given point within the pulsation waveform of the extracranial blood pressure (e.g., when the given point within the pulsation waveform corresponds to a selected point such as the minimum value of the cerebral blood flow value within the pulsation waveform of the cerebral blood flow). The control device may be configured to determine an indication of the intracranial blood pressure of the subject based on a specified critical closing pressure of the blood vessels within the subject's brain tissue. The critical closing pressure may include the value of the pressure at which the blood vessels within the subject's brain tissue close. For example, the control device may be configured to detect the closing of the blood vessels based on a change in the cerebral blood flow data (e.g., the cerebral blood flow value decreases to a zero value or a known minimum value, etc.). The control device may be configured to identify the point at which the blood vessels within the pulsation waveform of the brain close. The control device may be configured to identify the corresponding point within the pulsation waveform of the extracranial pressure. The control device may be configured to determine the ICP based on the corresponding pressure due to the blood vessels (by the surrounding ICP causing the blood vessels to close).

[0012] The control device may be configured to process data indicating the combined optical signal in order to obtain cerebral blood flow index data of the blood flow through the subject's brain tissue. The pulsation waveform of one or more specified pulses of the blood flow through the subject's brain tissue may include the pulsation waveform of the cerebral blood flow index. For example, the cerebral blood flow data may include a series of values of the cerebral blood flow index ( "CBFi"), for example, a series of cerebral blood flow index values in chronological order. The control device may be configured to determine ICP based on one or more characteristics related to these CBFi values. For example, the characteristics may be related to characteristics indicating the shape of the pulsation waveform, for example, the shape of each pulse. The characteristics may include at least one indication such as a maximum value and / or a minimum value, a difference between the maximum value and the minimum value, an average and / or a variance for a plurality of values, a rate of change of the values, and the like.

[0013] The detection device may be configured to obtain extracranial blood flow data using an iNIRS system. The iNIRS system may be configured to obtain both extracranial blood flow data and cerebral blood flow data using the same light source-detector channel. The iNIRS system may be configured to obtain extracranial blood flow index data. The control device may be configured to process the extracranial blood flow index data in order to obtain a value of the extracranial blood pressure. The optical detection device may be configured to be coupled to the subject's scalp so as to obtain a combined optical signal including both (i) a component of the beat frequency related to the sample light transmitted from the subject's brain tissue and (ii) a component of the beat frequency related to the sample light transmitted from the extracranial region of the subject's body. The control device may be configured to separate data related to the subject's brain tissue from data related to the extracranial region of the subject's body (for example, separate data from the same combined optical signal into two separate data groups, a group of intracranial data and a group of extracranial data). The control device may be configured to separate the data based on the flight time of the sample light. The control device may be configured to determine cerebral blood flow data and extracranial blood flow data based on the separated data.

[0014] The iNIRS system may include a plurality of photodetectors. Each photodetector may be configured to acquire cerebral blood flow data of the subject's brain tissue. The control device may be configured to obtain an indication of intracranial blood pressure based on the characteristics of the pulsation waveform of the blood flow pulse passing through the subject's brain tissue detected by the plurality of detectors. The device may be configured to acquire extracerebral blood flow data of different extracerebral regions of the subject's body based on the combined optical signals associated with different detectors. The detectors may be arranged to be spatially dispersed around the subject's scalp such that at least a portion of the blood flow pulse detected by different detectors is from different parts of the subject's brain tissue. The iNIRS system may include two light source-detector channels: (i) an intracranial light source-detector channel configured to acquire cerebral blood flow data, and (ii) an extracerebral light source-detector channel configured to acquire extracerebral blood flow data. The optical detection device may include an extracerebral blood flow sensor configured to acquire extracerebral blood flow data. The extracerebral blood flow sensor may be configured to acquire the pressure value of the extracerebral blood flow pulse.

[0015] The control device may be configured to obtain an indication of intracranial blood pressure based on the difference between the diastolic value and the systolic value of one or more pulses of blood flow through the subject's brain tissue. The control device may be configured to obtain an indication of intracranial blood pressure based on the pulsatility coefficient of the pulses of blood flow through the subject's brain tissue. The control device may be configured to obtain an indication of the subject's intracranial blood pressure based on the difference in shape between (i) one or more pulses of blood flow through the subject's brain tissue and (ii) one or more pulses of blood flow through an extracranial region of the subject's body. The control device may be configured to obtain an indication of the subject's intracranial blood pressure based on the diastolic value of the pulses of blood flow. The iNIRS system may include two or more light sources, where the first light source is configured to emit light passing through a plurality of wavelengths above the isosbestic wavelength for oxygen measurement (e.g., wavelength-scanned), and the second light source is configured to emit light passing through a plurality of wavelengths below the isosbestic wavelength for oxygen measurement (e.g., wavelength-scanned). The control device may be configured to obtain an indication of intracranial blood pressure based on the sample light received from each of these two light sources.

[0016] The control device may be configured to obtain time-of-flight data based on the combined optical signal, where the time-of-flight data includes a data surface that includes a distribution of a series of chronological time-of-flights of photons of sample light from the light source reaching the photodetector. The control device may be configured to obtain cerebral blood flow data based on the changes in the data surface. The control device may be configured to obtain cerebral blood flow data based on the attenuation rate associated with the data surface. The control device may be configured to obtain an indication of one or more optical properties of the subject's brain tissue based on the time-of-flight data. The one or more optical properties of the subject's brain tissue may include a scattering coefficient and / or an absorption coefficient. The control device may be configured to obtain cerebral blood flow data of the subject's brain tissue based on (i) one or more optical properties of the subject's brain tissue and (ii) the change in the intensity of the sample light received at the photodetector.

[0017] In one aspect, a non-invasive intracranial pressure detection method is provided, the method comprising: operating a light source to emit light (e.g., wavelength-swept); delivering (i) light from the light source through a sample channel towards the subject's brain tissue and (ii) light through a reference channel; receiving, in an interferometric light detector, (i) reference light from the reference channel and (ii) sample light from the subject's brain tissue, the sample light including light emitted from the light source; combining, in the interferometric light detector, the sample light and the reference light to provide a combined optical signal including one or more components of the beat frequency between the sample light and the reference light; and processing data indicative of the combined optical signal to obtain an indication of the subject's intracranial blood pressure based on at least one characteristic of the pulsatile waveform of one or more identified pulses of blood flow through the subject's brain tissue.

[0018] In one aspect, a non-invasive intracranial pressure detection device having an interferometric near-infrared spectroscopy (iNIRS) system is provided, the iNIRS system comprising: a light source configured to emit coherent light (e.g., wavelength-scanned); a sample delivery channel arranged to be coupled to the subject's scalp for coupling light from the light source and directing the light towards the subject's brain tissue; a reference channel coupled to the light source for receiving light from the light source; a light emitting device comprising the reference channel; a light detection device configured to be coupled to the subject's scalp and the light emitting device, the light detection device comprising an interferometric photodetector configured to receive (i) reference light from the reference channel and (ii) sample light from the subject's brain tissue, the sample light including light emitted from the light source, the photodetector being arranged to couple the sample light and the reference light to provide a combined optical signal including one or more components of the beat frequency between the sample light and the reference light; a signal processing and conversion circuit coupled to the detector and configured to generate combined optical signal data from the combined optical signal; a control device configured to process the combined optical signal data to obtain time-of-flight data including a distribution of the plurality of time-of-flight of photons of the sample light from the light source reaching the photodetector, process the time-of-flight data to obtain an indication of one or more optical properties of the subject's brain tissue, and determine cerebral blood flow data of the subject's brain tissue including an indication of one or more pulses of blood passing through the subject's brain tissue based on (i) one or more optical properties of the subject's brain tissue and (ii) a change in the intensity of the sample light received at the photodetector, and determine an indication of the intracranial blood pressure of the subject based on the shape of one or more pulses of blood flow passing through the subject's brain tissue.

[0019] Aspects of the present disclosure include one or more computer program products having computer program instructions for programming a processor to control the operation of an interferometric near-infrared spectroscopy system to control the operation of, for example, a light emitting device and a light detection device to perform any of the methods disclosed herein.

[0020] Embodiments may provide an iNIRS system and a method for neuroimaging and analyzing the brain tissue of a subject. The iNIRS system and method of the present disclosure are directed to a method for neuroimaging and analysis that is fundamentally different from the aforementioned fNIRS technology. Embodiments may provide an improved method for iNIRS neuroimaging and analysis. As disclosed herein, the iNIRS system of the present disclosure includes two light sources and one or more photodetectors. Further, the iNIRS system of the present disclosure may include a control device arranged to receive output signals from one or more photodetectors.

[0021] Each light source may include a light generation element arranged to generate light (e.g., near-infrared light). For example, each light generation element may include a laser. Each light source may include an optical device coupled to the light generation element. The optical device of each light source may be configured to deliver the light generated by the light generation element to one or more different locations. The optical device of each light source may be arranged to direct a portion of the light from the light generation element towards the region to be sampled. The optical device of each light source may be arranged to send a portion of the light to each photodetector. The optical device of each light source may include a plurality of light delivery channels. The plurality of light delivery channels may include one or more sample delivery channels and / or one or more reference delivery channels. Each light delivery channel may include an optical channel such as an optical fiber. Each light delivery channel may be configured to transmit light (e.g., from the light generation element towards the subject's scalp or the photodetector) along its length. The optical device of each light source may include an optical splitter configured to split the light into each of the different delivery optical channels.

[0022] The iNIRS system may be arranged such that when installed on the subject's head (e.g., to provide neuroimaging and analysis of the subject's brain tissue), the optical device of each light source is configured to send a portion of the light towards the subject's scalp. For example, the optical device of each light source may include a sample delivery channel (e.g., usable to send sample light towards the subject's scalp). The iNIRS system may be arranged such that when in use, the optical device of each light source is arranged such that a portion of the light can be sent directly to the photodetector (e.g., to combine with sample light from the subject's brain tissue). For example, the optical device of each light source may include a reference delivery channel (e.g., usable to send reference light to one or more photodetectors). The optical device of each light source may be configured to deliver light from the light generating element to each optical channel. The optical device of each light source may be configured to deliver both (i) light to the sample light delivery channel ("sample light") and (ii) light to the reference delivery channel ("reference light"). For example, the optical device of each light source may include an optical splitter configured to split the light received from the light generating element into respective different channels.

[0023] When the iNIRS system is installed and used in the subject's brain tissue, the sample light may be sent towards the subject's scalp and brain tissue (e.g., through a sample delivery channel), and the reference light may be arranged to be sent towards each photodetector (e.g., through a reference delivery channel). Each light source may be arranged to emit light (e.g., wavelength-swept). For example, each light source may be arranged to output light at a plurality of different wavelengths during a selected period. For example, each light source may include a changing element that controls the operation of the light generation element to output light at a plurality of different wavelengths respectively. Each light source may be arranged to sweep the wavelength of the light it outputs (e.g., the wavelength increases or decreases). Each light source may be arranged to emit chirped light where each chirp (or "pulse") includes one wavelength sweep. Each light source may be arranged to output continuous chirps with the same wavelength sweep such that the wavelength of the light output from the light source changes according to a repeating pattern.

[0024] Each photodetector may provide an interferometric photodetector. Each photodetector may include an optical device. The optical device of the photodetector is configured to send the detected light (e.g., from the subject's scalp) to the photodetector. The optical device of the photodetector may include a plurality of light receiving channels. The plurality of light receiving channels may include one or more sample light receiving channels and / or one or more reference light receiving channels. Each light receiving channel may include an optical channel such as an optical fiber.

[0025] The iNIRS system may be arranged such that when placed on a subject's head (e.g., to provide neuro-imaging and analysis of the subject's brain tissue), the optical device of the photodetector is configured to receive light emitted from a light source (e.g., light transmitted through the subject's brain tissue from the light source). For example, the optical device of the photodetector may include a sample light receiving channel (e.g., which can be used to receive sample light from each light source that has passed through the subject's brain tissue). The iNIRS system may be arranged such that when in use, the optical device of the photodetector is positioned to receive a portion of the light from each light source transmitted directly from the light source (e.g., transmitted along an optical channel). For example, the optical device of the photodetector may include a reference light receiving channel (e.g., which can be used to receive reference light from one or more light sources). Each photodetector may be coupled to each light source such that the reference delivery channel of the light source is coupled to the reference light receiving channel of the photodetector (e.g., such that reference light is transmitted from the light generating element to the photodetector via the reference delivery channel and the reference light receiving channel).

[0026] The optical device of the photodetector may be configured to deliver both (i) light from the sample light receiving channel ("sample light") and (ii) light from the reference light receiving channel ("reference light"). For example, when in use, the detector is arranged to receive both (i) sample light that has passed through the subject's brain tissue from each light source and (ii) reference light transmitted to the photodetector along one or more reference channels from each light source.

[0027] The photodetector may be arranged to combine the reference light and the sample light in order to provide a combined optical signal. For example, the photodetector may include an optical coupler (e.g., for combining the light of the reference light receiving channel and the light of the sample light receiving channel). The combined optical signal may include, for example, a plurality of components of a beat frequency that is a frequency corresponding to the wavelength difference between the sample light and the reference light. Each photodetector is configured to convert the received combined optical signal into one or more electrical signals indicative of the combined optical signal. For example, the detector may include one or more photodiodes. Each photodiode may output an electrical signal (e.g., a current) indicative of the combined optical signal. The detector may include a balanced photodetector (e.g., including two photodiodes that may be 180° out of phase with each other, and the output thereof is the combination of the current outputs of the two photodiodes). The detector may optionally include a current-voltage conversion circuit and / or one or more amplifiers for amplifying the electrical signal.

[0028] The iNIRS system may include at least one analog-to-digital converter arranged to convert an electrical signal (e.g., a combined optical signal) representing the sample light into one or more digital signals. The control device is arranged to process the digital signals in order to determine one or more characteristics of the subject's brain tissue. The control device may be configured to determine the optical characteristics (e.g., with respect to absorption and / or scattering) of the subject's brain tissue. The control device may be configured to determine one or more dynamic characteristics of the subject's brain tissue (e.g., characteristics that change over time of the subject's brain tissue). For example, the control device may be configured to detect the presence of movement (e.g., due to movement such as blood flow in the brain tissue) within the subject's brain tissue.

[0029] The control device may be configured to process digital signals in order to obtain information on the flight time of photons of the sample light transmitted from each light source through the subject's brain tissue to the photodetector. The control device may be configured to identify the penetration depth (and optionally the expected trajectory of the photons passing through the brain tissue) associated with different flight times of the photons of the sample light. The control device may be configured to obtain a distribution of a series of flight times in chronological order of the photons of the sample light reaching each photodetector. The control device may be configured to process a chronological series in order to identify changes over time in the distribution of flight times, such as the identification of attenuation and / or attenuation rate between the distributions of successful flight times. The control device may be configured to provide depth-resolved processing, for example, by applying the flight time data to a filter to focus only on the photons within a selected flight time range (e.g., to identify changes in the optical properties of the brain tissue with respect to the penetration depth associated with the flight time range). The control device may be configured to process the data received from the photodetector in order to provide flight time information together with depth-resolved autocorrelation for the subject's brain tissue.

[0030] The control device may be configured to process the received light data indicating the sample light received by the photodetector and output a control signal based on the received light data. The control signal may provide an indication of the distribution of flight times (for example, the control device may be configured to output the distribution of flight times). The control signal may provide an indication of one or more characteristics, such as the optical characteristics of the brain tissue, determined based on the flight time distribution (for example, the scattering coefficient and / or absorption coefficient, and / or how these coefficients have changed / are changing). The control signal may provide an indication of the blood flow in the subject's brain tissue. The control signal may provide a depth-resolved indication of one or more characteristics of the subject's brain tissue (for example, related to a specific region, such as within a selected penetration depth range in the subject's brain tissue). The control signal may include an indication of one or more characteristics of the subject's brain tissue, such as intracranial pressure, blood flow index, arterial elasticity, cerebral metabolic rate of oxygen consumption, etc. The medical characteristics may be related to a specific region / depth within the subject's brain tissue. The control signal may include an actuation command for a brain-computer interface, for example, to control the operation of the device based on the actuation command. The control signal may include an image for display, and the image represents a part of the subject's brain tissue (determined based on the received sample light).

Brief Description of the Drawings

[0031] Some examples of the present disclosure will now be described by way of example with reference to the drawings.

[0032]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 3C

Figure 4A

Figure 4B

[0033] In the drawings, like reference numerals are used to indicate like elements.

DETAILED DESCRIPTION OF THE INVENTION

[0034] The present disclosure relates to non-invasive monitoring of intracranial pressure (“ICP”). An interferometric near-infrared spectroscopy (“iNIRS”) system is used to acquire time-of-flight data for photons of light transmitted from a light source to a photodetector (at least some of such photons are transmitted through the subject's brain tissue). Based on the temporal evolution of this time-of-flight data, one or more characteristics related to the blood flow in the subject's brain tissue may be identified. In particular, the pulsation waveform for the pulsation of blood flow through the subject's brain tissue may be identified. An indication of ICP for the subject's brain may be determined based on one or more characteristics of this pulsation waveform. To further improve ICP accuracy, one or more characteristics of extracranial blood flow may also be acquired, and these characteristics may be compared with the characteristics of intracranial blood flow. The iNIRS system may be configured to acquire both intracranial blood flow data and extracranial blood flow data. An indication of ICP may be determined based on the difference between the pulsation waveform of intracranial blood flow and the pulsation waveform of extracranial blood flow. Such a difference may indicate a damping force for the pulsation of intracranial blood flow that does not exist for extracranial blood flow (this is, for example, because the volume of the skull is constant).

[0035] Interferometric near-infrared spectroscopy (“iNIRS”) Figure 1 shows a schematic diagram of an interference-type near-infrared spectroscopy (「iNIRS」) system 10. The iNIRS system 10 includes a light source 20, a plurality of photodetectors 30, and a control device 40. The inset A in Figure 1 shows a more detailed view of one of the photodetectors 30.

[0036] The iNIRS system 10 includes a light source modifier 22 and an optical splitter 24. The iNIRS system 10 includes a sample delivery channel 25 and a reference delivery channel 26. The iNIRS system 10 is shown to be coupled to the subject's head 2. The iNIRS system 10 includes a sample delivery probe 25a and a plurality of sample receiving probes 35a. For each photodetector 30, there is an associated sample receiving probe 35a, a sample receiving channel 35, a reference delivery channel connection 28, and a reference receiving channel 36.

[0037] The light source modifier 22 may include a source that supplies a variable electrical control signal (e.g., a device that supplies a variable current or voltage). The light source modifier 22 is coupled to the light source 20. The light source modifier 22 may be electrically connected to the light source 20 to supply a variable current / voltage to the light source 20.

[0038] The light source 20 may include a laser. For example, the laser may be a distributed feedback laser (「DFB」) or a MEMS vertical cavity surface emitting laser (「MEMS-VCSEL」). The light source 20 is coupled to the optical splitter 24. The optical splitter 24 has an input for receiving light from the light source 20. The optical splitter 24 has two outputs for transmitting the light from the light source 20 to two separate channels. The sample delivery channel 25, like the reference delivery channel 26, is coupled to the optical splitter 24 (to receive light from the optical splitter 24). The sample delivery channel 25 couples the optical splitter 24 to the sample delivery probe 25a. The sample delivery probe 25a is placed at a location on the subject's scalp.

[0039] Suitable other types of lasers include distributed Bragg reflector lasers (“DBR”), Fourier domain mode locked lasers (“FDML”), and vertical cavity surface emitting lasers (“VCSEL”). Further, or alternatively, pulsed supercontinuum lasers may be used in combination with a pulse stretching mechanism such as a diffraction grating, a GRISM pulse stretcher, or the length of a dispersive optical fiber. For example, such an apparatus may be configured to temporally separate wavelengths within a pulse such that a frequency chirped pulse is created (e.g., when comparing a sample pulse and a reference pulse, ultimately to provide an interferogram).

[0040] The reference delivery channel 26 is coupled to each of the optical detectors 30 by an optical splitter 24. At each detector, the reference delivery connection 28 couples the reference delivery channel 26 to a reference receiving channel 36 for the detector. Each reference receiving channel 36 is coupled to an optical detector 30 for the channel. Each optical detector 30 is connected to the light source 20 to directly receive reference light from the light source 20 (via one or more reference channels). Each sample receiving probe 35a is placed on the scalp of a subject. Each sample receiving probe 35a is coupled to a sample receiving channel 35. Each sample receiving channel 35 is coupled to an optical detector 30 for the channel. Each optical detector 30 is connected to indirectly receive sample light from the light source 20 (via the sample delivery channel and the sample receiving channel, and through the subject's brain tissue between those channels).

[0041] A plurality of different photodetectors 30 exist. Each detector may comprise an interferometer such as a Mach-Zehnder interferometer. Each of the different photodetectors 30 is coupled to the same light source 20 (each via one or more reference channels). The photodetectors 30 may be spatially separated from the light source 20. Also, the photodetectors 30 may be spatially separated from each other, or may be arranged on regions of the tissue that are sufficiently similar so that the received signals can be combined and averaged. For the reference light to reach the photodetectors 30 from the light source 20, the reference light is transmitted directly along one or more reference channels. For the sample light to reach the photodetectors 30 from the light source 20, the sample light is transmitted indirectly through the subject's brain tissue. The sample light is delivered to the subject's scalp via one or more delivery channels. Then, the sample light may pass through the subject's brain tissue and be received by being transmitted to the photodetectors 30 via one or more sample light receiving channels 35. Therefore, the subject's brain tissue may be illuminated using different optical channels for detecting light from the subject's brain tissue.

[0042] The control device 40 may comprise any suitable components having a data receiving function and a processing function. For example, the control device 40 may comprise at least one application specific integrated circuit ("ASIC"). Other examples of the control device 40 include a field programmable gate array ("FPGA"), and / or a data acquisition module ("DAQ"). The control device 40 is coupled to each of the detectors. The control device 40 may be connected to each detector via a wired connection (to receive an electrical signal indicative of the detection from the detector), and / or the connection may be wireless (to receive transmitted data indicative of the detection from the detector). The control device 40 is coupled to the light source modifier 22. This connection may be wired or wireless.

[0043] The iNIRS system 10 may be at least partially housed within a garment for the subject's head 2. For example, the iNIRS system 10 may be provided within a hat with a brim / hat without a brim worn by the subject on their head 2. The head garment may be arranged to hold the light source 20 and the detector in a fixed arrangement with respect to the subject's scalp. Some or all of the components may be provided with the head garment. For example, the head garment may include a plurality of receiving portions for housing the light source 20 and the photodetector 30. The channel connecting the light source and the photodetector 30 may be provided as part of the head garment (e.g., may be passed through a corresponding channel receiving portion of the head garment). The control device 40 may be separated from the head garment (and, for example, connected wirelessly), or may be provided as part of the head garment (e.g., by an ASIC in the head garment that may be wired to the detector and / or the light source modifier 22). For example, the garment may be configured to house the light source, the detection channel, the probe, and the other components of the system arranged somewhere together.

[0044] Some or all of the channels of the iNIRS system 10 may be provided by optical fibers. The optical splitter of the present disclosure may include a splitter of optical fibers. The iNIRS system 10 may, as relevant, include a lens and a reflecting device and / or a refracting device for beam steering. For example, the sample delivery probe 25a may include one or more lenses that spatially distribute the sample light from the sample delivery channel 25 towards the subject's brain tissue. As another example, one or more of the sample receiving probes 35a may include a lens that collects the received light into the sample receiving channel 35 connected to the sample receiving probe 35a. As another example, the probe may be a cut and / or polished bare fiber.

[0045] The iNIRS system 10 is arranged to provide a plurality of light source-detector pairs for each light source 20. That is, the iNIRS system 10 is arranged such that each photodetector 30 can receive two forms of light, namely, (i) reference light and (ii) sample light. Each detector is arranged to receive the reference light directly from the light source 20 (the reference light is transmitted from the light source 20 to the photodetector 30 along one or more channels, for example, without passing through the subject's brain tissue). Also, each detector is arranged to receive the sample indirectly from the light source 20 (the sample light is sent towards the subject's scalp tissue, but a part of the sample light may be transmitted through the subject's brain tissue on the way to the detector, for example, the sample light does not transmit only through the optical channel between the light source 20 and the photodetector 30).

[0046] The detector 30 is arranged on the subject's scalp to provide imaging of a selected region of the subject's brain. At least a part of the detector 30 is arranged to be spatially separated from the light source 20. One or more (for example, each) of the photodetectors 30 may be arranged to be sufficiently separated from the light source 20 such that at least a part of the photons of the sample light from the light source 20 received by the photodetector 30 penetrate into the subject's brain tissue. For example, the spacing between the light source and the detector may be selected such that the photodetector 30 receives photons of the sample light that have experienced many scattering events (for example, when transmitted through the subject's head 2, scattered many times between the light source and the detector). That is, the spacing between the light source and the detector may be selected such that the photodetector 30 receives photons that penetrate deeply into the subject's brain tissue. Such photons may have a longer flight time from the light source to the detector compared to photons that penetrate more shallowly and experience fewer scattering events.

[0047] Detector 30 may be arranged spatially close to each other on the subject's scalp. The arrangement of detector 30 may be selected such that the detectors image similar regions of the subject's brain. For example, detector 30 may be arranged within a threshold distance from each other on the subject's scalp so that it can average the data it acquires (e.g., to provide an average value for the same volume of the subject's brain). That is, detector 30 may be arranged to spatially survey the same volume of tissue in the subject's brain. For example, the detectors may be arranged within one attenuation length (e.g., within the sum of the absorption coefficient and the scattering coefficient) with respect to each other's tissue.

[0048] Light source 20 is arranged to generate light and direct this light towards the subject's scalp and (via the reference channel) towards photodetector 30. Optical splitter 24 receives the light generated by light source 20 and is arranged to split this light into two channels, namely, (i) towards the subject's scalp using sample delivery channel 25 and sample delivery probe 25a, and (ii) towards photodetector 30 using reference delivery channel 26 and reference light receiving channel 36. The splitter is configured such that most of the light is sent towards the subject's scalp. For example, the splitter may be a 90:10 splitter, or a 99:1 splitter. Sample delivery channel 25 receives the sample light from the splitter and is arranged to deliver this sample light towards the subject's scalp (via sample delivery probe 25a). Reference delivery channel 26 receives the reference light from the splitter and is arranged to deliver this reference light towards the detector (via reference light receiving channel 36).

[0049] Each reference delivery connection part 28 is arranged to deliver a part of the reference light transmitted along the reference delivery channel 26 to one of the reference light receiving channels 36. Each reference light receiving channel 36 is arranged to deliver the reference light to the optical detector 30 for the channel. The sample light receiving probe 35a is arranged to receive sample light from the subject's brain tissue. The sample light receiving probe 35a may collect the received sample light into the sample light receiving channel 35. The sample light receiving channel 35 is arranged to deliver the received sample light to the optical detector 30 for the channel. The sample light receiving probes 35a may be arranged extremely close to each other spatially on the subject's scalp.

[0050] Each detector is arranged to receive two inputs, namely, (i) directly the reference light from the light source 20, and (ii) indirectly the sample light from the light source 20 (e.g., transmitted through the subject's brain tissue and through the skin and skull of the subject's scalp). For example, each detector may include two or more input ports. The first input port of the detector may be coupled to the reference delivery channel 26 for the detector. The second input port of the detector may be coupled to the sample delivery channel 25 for the detector. The detector is arranged to combine (as an interferometer) the reference light and the sample light. The detector and the control device 40 are arranged to determine one or more characteristics of the subject's brain tissue based on this combined reference light and sample light (as will be described in more detail below).

[0051] The light source 20 is configured to emit light with a wavelength sweep. For this reason, the light source 20 may be configured to emit a series of light pulses. In each pulse, the wavelength of the light may be "swept" over a wavelength range. For example, the sweep may be in the form of a chirped pulse. The light is emitted at a plurality of different wavelengths within one pulse. For example, the wavelength may continuously increase or decrease within one pulse (the rate of change of the wavelength may be constant or variable). A series of chirped pulses may be continuous (e.g., the time interval between pulses is zero). The light source 20 may be configured to continuously emit a series of pulses in which each pulse has a wavelength sweep. However, it will be understood that the light source 20 does not need to provide a continuous sweep. For example, the light source may be adjusted stepwise rather than continuously, such that the light source 20 emits light of different wavelengths at different time intervals (e.g., individual time intervals for emission at each of a plurality of wavelengths). The light source 20 may sweep in one direction (e.g., only increase or only decrease during one wavelength sweep), or may sweep in both directions (e.g., increase and decrease during one wavelength sweep). A one-direction sweep may be beneficial as it increases the number of photons detected per sweep.

[0052] The control device 40 may be configured to selectively control the wavelength sweep of the light source 20. The light source modifier 22 is arranged to control the wavelength emission of the light from the light source 20. For example, the light source modifier 22 may be arranged to apply a selected current (or voltage) to the light source 20 to select the wavelength emission from the light source 20. The wavelength sweep of the light source 20 may be controlled using the light source modifier 22 to apply a corresponding electrical signal to the light source 20. The control device 40 may be arranged to control the application of current / voltage to the light source 20 using the light source modifier 22 to provide a selected pattern for the wavelength of the light emitted by the light source 20.

[0053] The light source 20 may be controlled to wavelength sweep according to a selected pattern for scanning. For example, the light source 20 may sweep over a selected wavelength range of light, and / or the light source 20 may sweep over the wavelength of light according to a selected sweep profile (e.g., linear increase, sine curve, triangle, etc.). For example, the light source 20 may sweep according to a selected sweep speed or a selected total sweep time. The light source 20 is configured to wavelength sweep the light such that, during one wavelength sweep, light is sent through the sample delivery channel towards the subject's brain tissue (and also to the detector via the reference channel) at each of a plurality of different wavelengths. The wavelength of the light emitted by the light source 20 changes over time. Thus, an indication of the time when the light is emitted from the light source 20 may be determined based on the wavelength of the light.

[0054] The light source 20 may be configured to sweep over a selected wavelength range. For example, the light source 20 may be configured to sweep at an optical frequency exceeding a region of 50 GHz. For example, this may cause the light source 20 to emit light modulated at a plurality of different wavelengths, such as between 829.94 nm and 830.06 nm when centered at, for example, 830 nm, or between 1309.857 nm and 1310.143 nm when centered at, for example, 1310 nm. The light source 20 may be configured to sweep over a wavelength range of at least 0.025 nm, at least 0.05 nm, at least 0.075 nm, at least 0.1 nm, at least 0.11 nm, etc. (e.g., around the centered wavelength). The light source 20 may have high power, a long coherence time, and wide wavelength tuning without mode hopping. The light source 20 may have a relatively narrow linewidth and a longer coherence length, for example, because the light source 20 does not perform a sweep over a particularly large bandwidth.

[0055] The light source of the present disclosure may be configured to emit highly coherent light, which is, for example, substantially coherent light. It will be understood that the light source cannot emit completely coherent light and wavelength-swept light because light of different wavelengths changes phase at different speeds. The light source of the present disclosure may be controlled to sweep over a relatively narrow wavelength range compared to its absolute wavelength. That is, the difference between the maximum wavelength and the minimum wavelength for one wavelength sweep is relatively small compared to these wavelengths. Each light source may be configured to emit light (e.g., an electric field) whose phase does not change significantly over time.

[0056] The iNIRS system of the present disclosure receives sample light and reference light that both originate from the same light source. The light source of the present disclosure is configured to emit wavelength-swept sufficiently coherent light such that the sample light and the reference light received by the photodetector are in relatively similar phases to each other. Thus, the combination of the sample light and the reference light causes substantially constructive interference between the two waves (e.g., two streams of light waves have sufficiently similar phases such that the resulting combined optical signal includes a constructive combination of the two light waves). That is, the coherence length of the light source may not need to decrease due to multiple scatterings in the tissue until the contrast of the coherence or interference fringes falls below the noise level in the measurement.

[0057] For example, each light source of the present disclosure may include a laser. The laser may be selected, for example, based on its coherence length in order to enable constructive interference to occur between the sample light and the reference light as described above. That is, the iNIRS system is arranged such that the expected maximum delay in the flight time of the photons of the sample light (transmitted through the subject's brain tissue and received by the photodetector) with respect to the photons of the reference light (transmitted along one or more reference channels and received by the photodetector) is within the coherence period of the laser (for example, the difference in the optical path lengths between the sample light and the reference light is within the coherence length of the laser). Within this coherence period, the phase of the light emitted by the laser remains substantially stable even though the wavelength of the emitted light changes. Therefore, in the optical signal coupled at the photodetector, the loss of amplitude may not be present (for example, the interference occurring at the detector may be substantially completely constructive).

[0058] For example, the iNIRS system may be configured to have a coherence length, or coherence distance, of approximately 50 m in air, or a light source having a coherence length between 50 m and 100 m (a coherence period between 166 ns and 333 ns) may be selected. This specific range is not intended to be limiting, but rather it will be understood to exemplify an approximate range for the light source. The light source may be selected to have a coherence length that is at least twice the expected maximum difference in optical path lengths, or for example, the coherence length may be three or four times or more. By having a light source with a coherence length much larger than the optical path length, the measurement accuracy of the photons of the sample light that have experienced many scattering interactions within the subject's brain tissue may be improved.

[0059] The iNIRS system 10 is arranged such that the path lengths between the light source and the detector for the reference light and the sample light are different. That is, the iNIRS system 10 is arranged such that the average optical path length, or the expected optical path length, for the light transmitted from the light source 20 through the subject's brain tissue to each detector is different from the optical path length for the light transmitted from the light source 20 through the reference channel to the detector.

[0060] As understood in the context of the present disclosure, photons of the sample light sent towards the subject's brain tissue may be transmitted from the light source 20 to the light detector 30 via virtually innumerable different paths. The photons of the sample light may experience many scattering events, and thus may follow a very intricate path between the sample delivery probe 25a and the sample light receiving probe 35a. The iNIRS system 10 is arranged to provide neuroimaging and analysis at least in part based on activities within the subject's brain tissue. The flight time of the photons of the sample light from the light source 20 to the light detector 30 naturally increases as the path length traveled increases. Therefore, photons that are transmitted along a longer path and penetrate deeper into the subject's brain tissue take more time to reach the light detector 30. The longer the flight time of the photons of the sample light, the higher the likelihood that the photons have penetrated deeper into the subject's brain tissue.

[0061] The iNIRS system 10 is arranged such that the shortest flight time for photons of light to be transmitted from the light source 20 to the light detector 30 is for the photons of the reference light transmitted along the reference channel. The photons of the sample light have a longer flight time than this reference light. It is likely that the photons of the sample light that penetrate deepest into the subject's brain tissue have the longest flight time to the light detector 30.

[0062] The iNIRS system 10 is arranged to determine the distribution of the flight times of photons of the sample light (the "DTOF"). For this purpose, a time point spread function (the "TPSF") that is similar to the DTOF but includes an instrument response function (the "IRF") that can be removed later by filtering (e.g., by deconvolution and / or subtraction) using post-processing may be determined. Each of the determined DTOFs may provide a distribution indicating the flight times of all the photons of the sample light incident on the photodetector 30 at a given instant. The DTOF may include an ensemble average representing many of the incident photons (in each of a plurality of different TOF bins). The intensity of each TOF bin provides an indication of the number of photons incident at that TOF. The phase of the TOF bin (obtained, for example, using Fourier analysis) may represent the average phase of all the photons arriving at that TOF bin. As will be described in more detail below, a number of characteristics of the subject's brain tissue may be determined based on the DTOF data acquired for the subject's brain tissue. To acquire such data, the iNIRS system 10 is configured to acquire an interferogram for the combined reference light and sample light received at a given light source 20.

[0063] The iNIRS system 10 is arranged such that each photodetector 30 receives the sample light and the reference light and combines the two using an optical coupler. For example, each detector may provide an interferometer assembly configured to combine the reference light and the sample light (using both a sample light channel and a reference light channel) to obtain an interference pattern (interferogram).

[0064] The light source 20 is configured to emit substantially coherent light. The interference pattern resulting from the light from the light source 20 (acquired by each detector) may include a combined signal having components of a beat (or intermediate / difference) frequency corresponding to the wavelength difference between (i) the wavelength of the photons of the sample light received by the photodetector 30 in a given temporal instance, and (ii) the wavelength of the photons of the reference light received by the photodetector 30 in that given temporal instance. The reference light at one sampling interval should be a fairly narrow and uniform wavelength limited by either the laser's inherent linewidth or the optical frequency sweep rate, because the photons of the received reference light travel the same distance from the light source 20 to the photodetector 30 (through the reference channel). The sample light comprises photons of different wavelengths, and each wavelength of the sample light corresponds to the flight time of that photon (due to the wavelength sweep of the light source 20) and the path specific to that photon through the tissue. Therefore, the resulting interferogram includes a plurality of different beat frequencies (due to different differences in wavelength). Higher beat frequencies may correspond to photons with a greater flight time (more deeply penetrating photons) when the sample path is longer than the reference path.

[0065] Each photodetector 30 includes an optical coupler arranged to couple light and provide the coupled light (which may include one or more components corresponding to the beat frequency) to a signal processing circuit. Each detector may include a square-law detector. For example, each detector may be configured to create an interference pattern based on the optical frequency difference between an incident sample electric field and a reference electric field. For example, the intensity of the detected output is proportional to the square of the incident electric field, and the incident electric field is the sum of the sample electric field and the reference electric field. The intensity of the detected output (in the form of photocurrent) is equal to the square of the sum of the incident sample electric field and the reference electric field. Such detectors may include photodiodes, avalanche photodiodes, and / or high-speed line scan cameras, streak cameras, high-speed CCD or high-speed CMOS sensors. The detector may be a high-bandwidth detector. For example, the detector may be configured to resolve interference fringes at 100 MHz or higher, up to 1 GHz. The detector may include one speckle detector. For example, the optical fiber used in the detector may be single mode. When a multimode detector is used, the detector may include an array of square-law detectors, such as a photodiode array, a focal plane array, a high-speed line scan camera, a high-speed CCD array, etc. Also, the detector may include a balanced detector array. For example, the balanced detector array may be configured such that the reference light and the scattered light are coupled and split (e.g., evenly) for a pair of phase-shifted detectors, such as a fiber coupler or a beam splitter cube with 4 ports (2 inputs and 2 outputs, 50:50 ratio). The balanced detector may increase the signal-to-noise of the detected signal by removing the incoherent part of the signal. Also, the balanced photodetector may make full use of all the light transmitted through the interferometer to suppress common noise such as laser intensity noise.

[0066] That is, each photodetector 30 may include an optical coupler configured to couple the sample light and the reference light to provide a combined optical signal. The iNIRS system 10 is arranged to process the combined optical signal to obtain an indication of the intensity of the light incident on the photodetector 30 at a given instant (e.g., using optical heterodyne detection and / or balanced detection). The iNIRS system 10 is arranged to obtain such a plurality of indications, e.g., the photodetector 30 may be arranged to repeatedly obtain an indication of the intensity of the light incident on the photodetector 30. That is, the iNIRS system 10 is arranged to measure the phase or frequency shift between the photons of the light at the two inputs (reference and sample) of the detector and consider such a difference to be due to the characteristics of the brain tissue intervening with respect to the sample light.

[0067] The acquired interferogram may be Fourier analyzed (e.g., using FFT or IFT) to obtain an indication of the DTOF for the photons of the sample light incident on the photodetector 30, respectively. When a square-law detector is used, the intensity at the detector may be proportional to the square of the sum of the electric field intensities. By multiplying the rate of change of the optical frequency by the time delay, the frequency of the interference fringes present in each interferogram may be generated. That is, the Fourier transform of an interferogram containing a plurality of beat frequencies may be used to indicate the flight time of the photons associated with those beat frequencies present in the interferogram.

[0068] To obtain this data on the DTOF for the photons of the sample light, the photodetector 30 is arranged such that two light inputs (sample and reference) are coupled into a combined light beam. The photodetector 30 is arranged to convert the combined light beam into an electrical signal representative of the combined optical signal. The iNIRS system 10 comprises at least one digitizer arranged to receive the electrical signals indicative of the combined optical signal and to convert those electrical signals into digital data representative of the combined optical signal. This digital data may be processed to obtain one or more different characteristics of the subject's brain tissue for neuroimaging and analysis.

[0069] An example of an apparatus for converting the received optical signal into digital data is shown in the inset A of FIG. 1. The inset A shows the arrangement of components that can be used as the photodetector 30 of the present disclosure. Also, as shown in the iNIRS system 10 of FIG. 1, the detector 30 receives two inputs, namely, (i) reference light transmitted along the reference delivery channel 26 and the reference reception channel 36, and (ii) sample light received via the sample reception probe 35a and delivered to the detector via the sample reception channel 35.

[0070] As shown, the detector may comprise an optical splitter combiner 301, a first optical channel 302a, a second optical channel 302b, a balanced photodetector 303, a transimpedance amplifier 304, an amplifier 305, and an analog-to-digital converter ("ADC") 306. The ADC 306 is arranged to provide a digital signal output 307.

[0071] The optical branching coupler 301 is coupled to both the reference receiving channel 36 and the sample receiving channel 35. The optical branching coupler 301 is arranged to receive both the sample light and the reference light and combine these two to provide a combined optical signal. The optical branching coupler 301 is arranged to split this combined optical signal into two separate channels, namely the first optical channel 302a and the second optical channel 302b. For example, this may be a 50:50 (or thereabouts) split. The first optical channel 302a and the second optical channel 302b are coupled to the balanced photodetector 303. Each optical channel sends light towards the associated photodiode. The balanced detector is arranged to provide an output based on the difference between the outputs from the two photodetectors. The two photodetectors are typically provided such that the beat signals on each photodiode are 180° out of phase with each other and the coherent AC terms are combined positively with each other. The balanced photodetector 303 is arranged to output a current corresponding to the difference between the output currents of the two photodetectors. The balanced photodetector 303 may remove unwanted DC terms such as the slow fluctuations originating from the light source 20 and other common mode effects such as noise from this signal.

[0072] The photodetector 30 is configured to convert the current output from the balanced photodetector 303 into a corresponding voltage using a current-voltage converter. As shown in the insertion diagram A of FIG. 1, the converter may include a transimpedance amplifier 304. Then, the voltage output from the transimpedance amplifier 304 is amplified using an amplifier 305. The amplifier may be used to expand the output signal to the full range of the ADC and further limit the electronic frequency of the circuit to maximize the SNR. Then, this amplified voltage is supplied to the ADC 306 for digitization. The ADC 306 includes a digitizer having a sufficient bandwidth so that the entire signal bandwidth including the time-of-flight information can be digitized without attenuation. For example, the bandwidth of the digitizer may be approximately the same as at least the bandwidth of the combined optical signals. For example, the digitizer may be selected to have a sufficiently high sampling rate such that the bandwidth of the signal being processed satisfies the Nyquist criterion. The digitizer may be provided as part of each photodetector 30, or the digitizer may be provided as part of the control device 40, and the control device 40 may be coupled to each of the photodetectors 30 to receive the electrical signals from the photodetectors 30 to be digitized. For each of the combined optical signals, a digital signal output 307 is provided that gives a digital representation of the combined optical signal (and the sample light incident on the photodetector 30 at the moment the combined optical signal is generated and measured).

[0073] The iNIRS system 10 is configured to obtain a plurality of digital signal outputs 307 indicative of sample light incident on the photodetectors 30. In particular, each photodetector 30 is configured to repeatedly combine optical signals (sample and reference) in order to provide a digital signal output 307 representative of each of the combined optical signals. For example, at each photodetector 30, a time-series digital signal output 307 may be obtained, and each subsequent digital signal output 307 is for the time point after the combined optical signal has been obtained and measured (and the digital signal output 307 represents that the combined optical signal has been obtained and measured). As described above, each of these signals may indicate the DTOF of the sample light at that point in the detector.

[0074] That is, the iNIRS system 10 is configured to obtain a plurality of time-ordered DTOFs for each of the plurality of different photodetectors 30. The digitizer may provide a digital output indicative of different measurements, and this digital output may optionally be processed in a number of ways to provide DTOF data. Examples of such processes are described hereinafter.

[0075] The control device 40 may be configured to receive raw digital interferogram data (e.g., data representing an interferogram obtained by converting a combined optical signal into digital data). The raw interferogram may be divided into individual sweeps for the wavelength-swept radiation from the light source 20. For example, the sweep speed of the light source 20 and the time at which the first sweep is initiated may be used to determine the sweep period. And the data may be divided into a plurality of groups, each group representing an individual sweep. At this stage, the Hilbert transform may optionally be performed on the data. Windowing may be performed (e.g., using a Hann window or a Blackman-Harris window) to reduce the sidelobes of the data. Either inverse or normal Fourier analysis may be performed on the data. For example, an inverse Fourier transform may be performed. Fourier analysis may be performed for each wavelength sweep of the light source 20. The resulting data may be in the form of a series of time point spread functions ("TPSF"), each TPSF corresponding to the associated wavelength sweep. The TPSF data may remove the instrument response function ("IRF") to provide DTOF data.

[0076] That is, the iNIRS system 10 may be configured to obtain a distribution of a series of time-ordered flight times of photons of sample light incident on each of a plurality of different detectors. This DTOF data may be processed to provide information related to many different physical characteristics of the subject's brain tissue. The DTOF data may be used to determine the optical characteristics of the medium through which the sample light is transmitted. Each TOF bin in the DTOF may represent a selected volume in the subject's brain, and each DTOF represents the total volume of tissue investigated by the photons (for example, each DTOF may represent a weighted average of the characteristics of the brain tissue and other tissues through which the photons are transmitted, such as the scalp and skull). Examples of optical characteristics include the scattering characteristics and absorption characteristics of the subject's brain tissue. The DTOF data may be used to determine dynamic characteristics of the subject's brain tissue, such as how certain characteristics change over time. This includes how optical characteristics and characteristics indicating movement within the subject's brain tissue (for example, due to blood flow) evolve over time. The iNIRS system 10 may be configured to perform a Fourier transform (for example, FFT) on the TOF distribution obtained to acquire gamma data, and a dynamic signal may be acquired from the temporal changes within the gamma signal.

[0077] A series of DTOFs in time order may correspond to the surface of the data in a three-dimensional volume. The surface may represent the DTOF for each subsequent (time-ordered) DTOF, and thus the surface indicates each individual DTOF and the temporal evolution of the DTOF. This surface may provide a large amount of data from which the characteristics of the subject's brain tissue can be determined. Analysis of the temporal variation over time (for example, decay of the DTOF value) in the DTOF value may provide an indication of one or more dynamic characteristics of the subject's brain tissue. That is, the analysis of decay is used to identify that one or more characteristics change within the subject's brain tissue and, optionally (for example, using the decay rate), to identify the rate at which these characteristics change. The order of decay of the DTOF (for example, decay with t, t 2 etc.) may be used to determine one or more characteristics of the type of movement (for example, diffusion or flow).

[0078] The control device 40 may store data associating the flight time of photons of the sample light with an indication of the average path trajectory of the photons. This data may include an indication of the depth of penetration of the photons into the subject's brain tissue and / or an indication of the region of the subject's brain tissue through which the photons passed when transmitted from the light source 20 to the photodetector 30. The control device 40 may be configured to process the DTOF data by dividing this data into selected flight time bins. Within each TOF bin, the data may provide depth-resolved evolution data for the subject's brain tissue. That is, the TOF may be related to a specific depth of penetration or region, and each TOF bin may contain data indicating characteristics related to a specific depth of penetration or region. The evolution of the data within each TOF bin may provide an indication of how one or more characteristics of the subject's brain tissue evolve. For example, when the evolution suggests a change in movement (e.g., blood flow), the movement may be specified as well as the region in which the movement occurs. For this reason, the TOF-resolved attenuation gradient may be used to specify how the curve decays over time for a specific TOF (e.g., for a specific depth of penetration / region).

[0079] That is, the iNIRS system 10 is configured to perform an autocorrelation in which the DTOF for successive wavelength sweeps is combined in order to estimate the temporal variation of the light irradiation field at the photodetector 30. The variation may be quantified due to the associated temporal variation in the DTOF. Also, the variation may be depth-resolved by identifying the associated TOF (and associated depth of penetration / region) in which the variation occurs.

[0080] The control device 40 may be configured to process the data received from the photodetector 30 in order to provide depth-resolved autocorrelation of the subject's brain tissue along with time-of-flight information. The control device 40 may be configured to use this information to obtain indications of a plurality of different characteristics of the subject's brain tissue, such as intracranial pressure ("ICP"), blood flow index, arterial elasticity, and the like. These characteristics of the subject's brain tissue are used in a plurality of different forms of neuroimaging and analysis, such as brain-computer interface, etc., to identify potential local damage or paralysis by imaging regions of the brain and / or to monitor neurological responses to substances such as drugs.

[0081] Intracranial pressure ("ICP") As described above, the iNIRS system 10 includes an optical interferometer arranged to combine the sample light and the reference light to provide a combined optical signal. The system 10 may detect the frequency of the light received by the detector. The received light (i.e., the combined optical signal) includes light of a plurality of beat frequencies between the sample light and the reference light. The iNIRS system 10 also includes a signal processing conversion circuit configured to be coupled to the detector 30 to create combined optical signal data from the combined optical signal (i.e., to create data indicative of the received combined optical signal).

[0082] The control device 40 of the iNIRS system 10 is configured to process the combined optical signal in order to acquire time-of-flight data including the distribution of the plurality of time-of-flight of photons of the sample light from the light source 20 reaching the photodetector 30. The control device 40 may be configured to process the combined optical signal data in order to acquire a data surface including the distribution of a plurality of temporally consecutive time-of-flights (e.g., a series of DTOFs in time order). The control device 40 may be configured to process this data surface in order to obtain an indication of autocorrelation decay. Each autocorrelation may provide an indication of how similar the first DTOF distribution is to the DTOF distribution preceding it (or further, how similar a portion of the first DTOF distribution is to the corresponding portion of the subsequent DTOF distribution having, for example, a portion representing a specific time-of-flight (“TOF”) bin). The autocorrelation decay may provide an indication of how the autocorrelation changes over time, e.g., how the autocorrelation is changing. That is, the control device 40 may be configured to obtain an indication of any temporal variation of the DTOF distribution acquired over time for the subject. The DTOF distribution may include data for each of a plurality of TOF bins. Some of these TOF bins (typically having longer times) may represent the volume of tissue in the subject's brain. The control device 40 may be configured to identify the temporal variation associated with one or more volumes of tissue in the subject's brain.

[0083] Also, the control device 40 is configured to obtain an indication of the scattering coefficient and the absorption coefficient of the subject's brain tissue. The control device 40 can determine these coefficients using the time-of-flight data (e.g., based on one or more of the acquired DTOFs). For example, the control device 40 may determine these coefficients based on one or more statistical moments (e.g., mean / variance) of the distribution of the DTOF (or TPSF) (or multiple such distributions), and / or based on the shape of the distribution of the DTOF (or TPSF) (or multiple such distributions).

[0084] The control device 40 is configured to obtain a cerebral blood flow index of the subject based on the acquired scattering coefficient, absorption coefficient, and self-correlation attenuation. For this reason, the control device 40 may be configured to regard the temporal variation of the volume of the subject's brain as being due to the movement of blood in that region. The cerebral blood flow index may provide a relative measurement of the movement occurring in the tissue in the subject's brain.

[0085] The control device 40 is configured to acquire cerebral blood flow data of the subject's brain tissue (i.e., the tissue in the subject's brain). The cerebral blood flow data may be obtained based on the detected changes occurring within the subject's brain tissue. The control device 40 may be configured to detect changes related to the blood within the subject's brain tissue. This change may be related to the flow of blood through the subject's brain tissue. That is, the control device 40 may be configured to detect a sign that blood is moving in a given region of the subject's brain by determining that it is uncorrelated in the subsequent DTOF distribution.

[0086] As described above, the control device 40 may be configured to obtain a cerebral blood flow index ("CBFi") of the subject's brain tissue. CBFi may provide a sign of movement occurring within the subject's brain. For example, CBFi may provide a relative measurement that describes the movement occurring within the subject's brain. The movement may be due to blood moving (e.g., flowing) through the subject's brain. CBFi provides a relative measurement. CBFi may include an indication of the average velocity in the bulk tissue. For example, the CBFi for a given volume in the subject's brain may provide an indication of the average velocity of the movement occurring within that volume. The movement may be due to the movement of blood, and thus, CBFi may provide an indication of the average blood flow velocity. For example, an increase in the value of CBFi may indicate an increase in the velocity occurring within the volume of the brain.

[0087] The iNIRS system may be sensitive to all forms of movement of blood through the subject's brain. For example, the blood flow monitored by the iNIRS system 10 may be for blood refluxed within the blood vessels in the brain tissue, such as in the microvascular system of the subject's brain tissue, and / or the blood flow may be for movement such as Brownian motion through the subject's brain tissue (rather than the flow of blood through large tubular structures such as veins and arteries). It will be understood that the exact form of the movement of blood detected by the iNIRS system is determined by the volume of tissue being investigated by the iNIRS system.

[0088] The iNIRS system 10 may be configured to measure an indication of the perfusion pressure of the blood flow within the brain tissue. Since the blood passes through such regions of the subject's brain tissue, the CBFi may provide an indication of the behavior of the blood.

[0089] The iNIRS system 10 may be configured to acquire data of the subject's brain tissue at a sufficiently high rate to identify changes in the blood flow through the subject's brain tissue. In particular, the iNIRS system 10 may be configured to acquire data at a sufficiently high rate to identify changes in the subject's blood flow caused by the beating of the subject's heart (e.g., to identify the systolic and diastolic characteristics of the blood flow). For example, the iNIRS system 10 may be configured to acquire data at a rate of at least 10 Hz, such as exceeding 20 Hz, for example, at a rate between 10 Hz and 100 Hz.

[0090] The control device 40 is configured to acquire cerebral blood flow data (i.e., data including an indication of the blood flow within the subject's brain tissue) including an indication of one or more pulses of the blood flow through the subject's brain tissue. The control device 40 may determine the CBFi for the subject's brain tissue, and the pulse of the blood flow through the subject's brain tissue is apparent in the CBFi determined for the subject's brain tissue. An example of such a determined CBFi is shown in FIG. 2.

[0091] Figure 2 shows an example of CBFi obtained for a subject's brain tissue that evolves over time. In Figure 2, the pulses shown as two pulses occur periodically and repeatedly (however, each individual pulse may vary in magnitude, shape, and the frequency at which the pulse occurs). Typically, each pulse comprises a diastolic CBFi value (e.g., a lower CBFi value) and a systolic value (e.g., a higher CBFi value). Within one pulse, CBFi may start at its diastolic value (its lowest value) and increase rapidly up to its systolic value (its highest value). Then, CBFi falls from its systolic value towards its diastolic value, but CBFi may increase temporarily at least once (or start to decrease at least at a slower rate) when falling from the systolic value to the diastolic value. Once it returns to the diastolic value, the process is repeated (due to the subject's heart beat).

[0092] The iNIRS system 10 is configured to use optical interferometry to obtain a measurement signal that enables the control device 40 of the iNIRS system 10 to obtain cerebral blood flow data indicating the behavior of blood flowing through the subject's brain tissue (e.g., the control device 40 may obtain the temporal evolution of CBFi values as shown in Figure 2).

[0093] As will be described in more detail below, the control device 40 is configured to process the cerebral blood flow data to determine an ICP indication for the subject's brain tissue. The control device 40 may be configured to determine the ICP based on one or more characteristics of the pulsatile waveform of the blood flow. For this purpose, the control device 40 may use any of a number of suitable characteristics. In an example, the characteristic may describe the shape of the pulsatile waveform or other relative measurement values associated with the pulsatile waveform.

[0094] The volume in which the subject's brain tissue is provided is limited by the subject's skull. The skull is typically very hard, so the subject's brain tissue is provided within a certain internal volume of the skull. Since this internal volume does not change, as the pressure within the skull increases, the substances within the internal volume are more compressed (and vice versa). This also applies to the pulse of blood flowing through the subject's brain tissue. In order for blood to flow through the subject's brain tissue, a part of the brain tissue needs to be compressed to create a place for the blood to pass through. The amount by which the subject's brain tissue can be compressed to receive blood flow is determined by the subject's ICP. For a given pulse of blood flow through the subject's brain tissue, the amount by which the brain tissue is compressed to receive the pulse of blood flow decreases as the ICP increases (since the brain tissue is already more compressed as the ICP increases). Similarly, a part of the blood flow may become slower (e.g., due to increased resistance to its movement), and / or the amount of blood flowing per unit time may decrease.

[0095] The control device 40 is configured to use the cerebral blood flow data to obtain an indication of the influence of ICP on the pulsatile waveform of blood flow through the subject's brain tissue. The control device 40 may be configured to identify changes in the pulsatile waveform, such as a changing shape, and / or a changing maximum / minimum value, and use this information to obtain an indication of the subject's ICP. For example, the control device 40 may be configured to obtain an indication of ICP based on the maximum CBFi value and / or the minimum CBFi value for a pulse of blood flow through the subject's brain tissue, and / or based on the difference between these values.

[0096] From this, an exemplary method for obtaining ICP will be described with reference to FIG. 2. As described above, FIG. 2 shows the CBFi values obtained using the iNIRS system 10 of the present disclosure for the pulsatile waveform of the blood flow pulse through the brain tissue of the subject. The control device 40 is configured to obtain an indication of, for each pulse, the systolic (e.g., highest) CBFi value of each pulse and the diastolic (e.g., lowest) CBFi value of each pulse. Both of these values are shown in FIG. 2. Further, the control device 40 is configured to obtain the average CBFi value for each pulse (also shown in FIG. 2). The control device 40 is configured to obtain a value of the pulsatility coefficient of cerebral blood flow based on the diastolic CBFi value, the systolic CBFi value, and the average CBFi value for the pulse. For example, the pulsatility coefficient of CBFi may be obtained by dividing the difference between the systolic CBFi value and the diastolic CBFi value by the average CBFi value for each pulse. The control device 40 may be configured to obtain an indication of ICP based on the obtained pulsatility coefficient of CBFi. For example, the control device 40 may utilize stored data (such as in a lookup table) that associates the value of the pulsatility coefficient of CBFi with the ICP value, or for example, use a known regression relationship between the pulsatility coefficient of CBFi and ICP.

[0097] Another exemplary method for obtaining ICP will now be described with reference to FIGS. 3A through 3C. In this method, an additional data stream is used in combination with the CBFi data acquired by the iNIRS system 10. The additional data stream includes data indicating one or more pulses of blood flow from different regions of the subject's body to the subject's brain tissue, which data is hereinafter referred to as extracranial blood flow data. The extracranial blood flow data is derived from a region of the subject's body that is not subject to the same constraint of a constant volume imposed by the subject's skull. This method includes comparing one or more characteristics of the pulsatile waveform of cerebral blood flow with the corresponding characteristics of the pulsatile waveform of extracranial blood flow. And an indication of ICP for the subject's brain tissue may be obtained based on the difference between the intracranial and extracranial pulses of the subject's blood flow (e.g., from the difference in the shape and / or values of the pulsatile waveforms).

[0098] Figure 3A is similar to Figure 2 in that it shows the CBFi values obtained using the iNIRS system 10 of the present disclosure for the pulsatile waveform of the blood flow pulse through the brain tissue of the subject. Figure 3B shows a graph that looks the same as Figure 3A, but this graph shows the pulse of the extracranial blood flow. The extracranial blood flow is for a part of the subject's body that is not subject to the constraint of a constant volume (similar to when it is inside the subject's skull). In such an extracranial region, each pulse of the blood flow has a pulsatile waveform in which the influence of the pressure acting from the surrounding tissue to the blood vessel is not very apparent. That is, in the blood vessels in the extracranial region, the tissue surrounding the blood vessel may only receive much smaller pressure fluctuations compared to the local pressure fluctuations that can occur inside the subject's skull (i.e., an increase in pressure does not correspond to a corresponding increase in volume). For example, the extracranial blood flow may be for the blood flow through a vein or artery of the subject, such as a vein or artery in the subject's scalp.

[0099] In the example of Figure 3B, the graph shows a plot of the arterial blood pressure over time (the "ABP") (rather than the cerebral blood flow index in Figure 3A). The ABP pulse waveform (Figure 3B) may appear relatively similar to that for the CBFi (Figure 3A). The control device 40 may be configured to temporally align the corresponding pulse waveforms of the intracranial and extracranial pulses of the blood. For example, the timing of the pulses may be offset for different regions of the body, and thus, it will be understood that the control device 40 may be configured to align the pulse in one region with the corresponding pulse in another region (such that the comparison of the two waveforms is made for the same pulse even if the measurements are made during a period when the pulses are slightly different).

[0100] In one example, the control device 40 may be configured to perform a comparison between different values (e.g., diastolic value, systolic value, and / or average value) for two pulses in the manner described above. In that case, the control device 40 may use the value of the extracranial blood flow to provide an indication of the reference pulsatility coefficient for the pulse of the subject's blood flow, and the difference between this reference pulsatility coefficient and the pulsatility coefficient of CBFi is considered to be the influence of ICP on the pulse of the blood flow through the subject's brain tissue (e.g., using a similar regression analysis that converts the difference in pulsatility coefficients between cerebral blood flow and extracranial blood flow into an indication of ICP).

[0101] Another example of determining ICP based on cerebral blood flow data and extracranial blood flow data is shown in FIG. 3C. In FIG. 3C, the cerebral blood flow data is plotted against the extracranial blood flow data, with CBFi shown on the y-axis and ABP shown on the x-axis. Two plotted data (i.e., cerebral blood flow and extracranial blood flow data) are arranged on the graph, and for example, the linear regions of those data substantially overlap each other (or at least are close to each other even when the plotted data do not completely overlap). As can be seen from FIG. 3C, there is a linear region from the point where the line intersects the x-axis (labeled "CrCP") to the region where the data branches and there is a loop-shaped region (labeled "overlapping hump"). As can be seen from FIG. 3C, the curve intersects the x-axis at a positive ABP value (i.e., the CBFi value is 0). The control device 40 of the iNIRS system 10 may be configured to process the intracranial data and the extracranial data to identify the value of this point (CrCP).

[0102] CrCP represents the critical closing pressure for blood vessels in the subject's brain tissue. As described above, CBFi provides information related to the movement of blood flow through the blood vessels in the subject's brain tissue. As the CBFi value decreases, this indicates a decrease in the movement of blood within the subject's brain tissue (e.g., a zero measurement value for CBFi may represent no blood flow). The intersection on the x-axis of the graph in FIG. 3C represents the value of the arterial pressure at which CBFi is zero (i.e., there is no blood flowing through the blood vessels in the subject's brain tissue). This is called the critical closing pressure because it is the pressure at which the small blood vessels in the brain "close". That is, the value of CrCP represents a situation where the pressure in that blood vessel is low enough such that the blood vessel is forced to close (due to the external pressure applied to that blood vessel).

[0103] The control device 40 is configured to determine which CrCP value is for one or more of the blood vessels in the subject's brain tissue. The control device 40 is configured to request an ICP instruction based on this CrCP value. A comparison between the arterial pressure and CBFi may provide an indication of the blood pressure (at the same / corresponding points in the pulsatile waveform) of the subject's artery when the blood vessels in the subject's brain tissue are closed. The ICP instruction may be requested based on this information (i.e., based on the pressure at which the blood vessel is "closed"). For example, the ICP may be requested as the external pressure that needs to be applied to the blood vessel to close it. This may include a vascular compliance term that represents the force applied to the blood by the blood vessel wall (to account for the fact that there are several blood pressures present in the blood vessel, such as the subject's arterial pressure).

[0104] This method is depicted in FIG. 3C, and it will be understood that the control device 40 need not create corresponding graphs (these graphs are shown for illustrative purposes of the method). The control device 40 may be configured to compare extracranial blood flow data (e.g., blood pressure data for one or more of the subject's veins / arteries outside the subject's brain tissue) with cerebral blood flow data (e.g., the CBFi values of one or more blood vessels in the subject's brain tissue). Based on this comparison, the control device 40 may be configured to identify the corresponding pressure (e.g., in the subject's vein / artery) at which the blood vessels in the subject's brain tissue are occluded. The control device 40 may be configured to determine an ICP indication based on this CrCP value (e.g., by determining the pressure within the subject's brain required to occlude the cerebral blood vessels).

[0105] In the method by which extracranial blood flow data is acquired, it will be understood that any suitable device may be used to acquire this data. For example, the iNIRS system 10 may be provided in combination with another detection element configured to acquire such data. The other detection element may be configured to measure blood pressure in another region of the subject's body, such as one of the subject's limbs, an arm, or the subject's hand / finger. The detection element may be configured to acquire data (e.g., diastolic values, and / or systolic values, and / or average values) that includes an indication of one or more characteristics of the pulsation waveform in that region of the subject's body. For example, the detection element may be configured to acquire an indication of how blood pressure changes over time within the pulsation waveform of the blood passing through the subject's vein / artery.

[0106] Furthermore, or alternatively, the iNIRS system 10 of the present disclosure may be configured to acquire both cerebral blood flow data and extracerebral blood flow data. For example, the iNIRS system 10 may acquire data representing cerebral blood flow and extracerebral blood flow (e.g., data for both cerebral blood flow and extracerebral blood flow may originally be included in one spectrogram / interferogram), and may include one light source-detector channel arranged to generate combined optical signals.

[0107] Figure 4A shows an example of an iNIRS system 10 arranged to provide such functionality.

[0108] The iNIRS system 10 of Figure 4A is similar to that of Figure 1 described above, and thus, repeated components will not be described again. As described above, the iNIRS system 10 is arranged to split light from a light source 20 (not shown) into a sample delivery channel 25 and a reference delivery channel 26 (by a beam splitter 24). The photodetector 30 then receives reference light (from the reference delivery channel 26) and sample light (from the sample receiving channel 35). The sample delivery probe 25a and the reference delivery probe 35a are also shown.

[0109] Figure 4A also shows different layers of the subject's head. The top layer is the scalp skin surface 101. The second layer under the scalp skin surface is the scalp tissue 102. The scalp tissue includes a plurality of arteries and veins. Under the scalp tissue is the subject's skull 103, and within the subject's skull is the brain tissue 104 arranged. The veins and arteries in the subject's scalp tissue are relatively less restricted by the subject's skull. That is, in this region of the subject's body, the veins / arteries are not hindered by the subject's skull from expanding in volume (whereas the blood vessels in the subject's brain tissue are hindered). Therefore, an increase in blood pressure in the veins / arteries may provide a corresponding increase in volume in these regions.

[0110] For photons of light that reach the subject's brain tissue from the light source 20 (and also through the sample delivery channel 25 and the sample delivery probe 25a), it is necessary to penetrate through the subject's scalp skin surface, scalp tissue, and skull. For photons of light to reach the veins / arteries in the subject's scalp tissue, there is no other way but to penetrate through the subject's scalp skin surface (and the relevant part of the scalp tissue). For the sample light from the light source 20 that reaches the detector 30, two exemplary photon paths are shown, namely, the shallow photon path 202 and the deep photon path 204. The deep photon path between the light source 20 and the light detector 30 is much longer than the shallow photon path (in order to transmit deeper into the subject's brain tissue). For both photon paths, there are many scattering events occurring in the subject's head. In this example, photons transmitted along the shallow photon path interact with at least one blood-transporting region (e.g., veins or arteries) of the subject's scalp tissue, and photons transmitted along the deep photon path interact with at least one blood vessel in the subject's brain tissue.

[0111] The light source 20 emits many more photons, and the paths for the photons to pass through the subject's head from the light source 20 to the detector 30 are different. The sample delivery probe 25a and the sample light receiving probe 35a are spatially arranged on the subject's scalp such that at least some of the photons of the sample light from the light source 20 that reach the detector 30 are transmitted along the shallow photon path and some are transmitted along the deep photon path. For example, the probes are spatially sufficiently separated so that several deep photon paths are generated.

[0112] Figure 4B shows the distribution of the flight times of the photons of the sample light received by the detector 30. As shown, the number of photons of the sample light is maximum for relatively short flight times, and the number of photons reaching at longer flight times decreases. As described above, the flight times of the photons of the sample light approximately correspond to their penetration depths. That is, photons that penetrate deeper have longer flight times than photons that penetrate shallower.

[0113] The time-of-flight distribution shown in FIG. 4B includes photons of the sample light that have traveled along a shallow path (and that can provide information related to extracerebral blood flow) and photons of the sample light that have traveled along a deep path (and that can provide information related to cerebral blood flow). As shown in FIG. 4B, photons of the shallow photon path have a shorter time of flight than photons of the deeper photon path. The control device 40 may be configured to obtain information about both cerebral blood flow and extracerebral blood flow within this single interferogram.

[0114] For this reason, the control device 40 is configured to separate cerebral blood flow from extracerebral blood flow. This may include the control device 40 separating cerebral blood flow data from extracerebral blood flow data based on the time-of-flight data. For example, the control device 40 may be configured to regard photons of the received sample light as being related to the subject's scalp tissue when the received photons have a time of flight that is less than a first threshold value. The control device 40 may be configured to regard photons of the received sample light as being related to the subject's brain tissue when the received photons have a time of flight that is less than a second threshold value. For example, the first threshold value and the second threshold value may be different (such that photons that are likely to have scattered from the subject's skull, for example, have a time of flight between the first threshold value and the second threshold value). That is, the control device 40 may be configured to obtain depth-resolved information about the photons of the received sample light. This depth-resolved information may include an indication of whether the photons have penetrated beyond the subject's skull. The control device 40 may select photons that do not penetrate the skull to obtain extracerebral data and photons that penetrate the skull to obtain intracerebral data.

[0115] The control device 40 may be configured to process cerebral blood flow data and extracerebral blood flow data separately. For example, the control device 40 may acquire time-of-flight data (e.g., including the measured distribution of time-of-flight) and separate this time-of-flight data into different data streams, namely, (i) an extracerebral data stream for photons with a shorter time-of-flight that are likely related to scalp tissue, and (ii) an intracerebral data stream for photons with a longer time-of-flight that are likely related to brain tissue. Each data stream may be processed individually in the manner described above to obtain blood flow index data including an indication of one or more pulses of blood (e.g., passing through veins / arteries in the subject's scalp or blood vessels in the subject's brain tissue) passing through the relevant region of the subject's body.

[0116] The control device 40 may be configured to process extracerebral blood flow data to obtain an indication of one or more characteristics of the pulsatile waveform of extracerebral blood flow (e.g., to obtain blood flow index data for the pulse of blood flowing through veins / arteries in the subject's scalp tissue). The control device 40 may be configured to determine pressure data for the flow of the pulse of blood passing through the subject's veins / arteries (as apparent from the blood flow index data acquired using the iNIRS system 10). For example, the control device 40 may store known conversion data for converting blood flow index values to corresponding pressure values (e.g., using a technique similar to the method of the CBFi pulsatility coefficient described above). The control device 40 may be configured to obtain extracerebral blood flow pressure data, e.g., data including pressure values for the pulses of blood flow in different periods in each pulsatile waveform of the pulse of blood flowing through the subject's scalp tissue. The control device 40 may use the extracerebral pressure data and the cerebral blood flow index data to obtain an indication of intracranial pressure (e.g., in the manner described above with respect to FIGS. 3A to 3C, such as specifying the CrCP value for the subject's brain tissue).

[0117] Accordingly, the iNIRS system 10 may be configured to acquire both intracranial data and extracranial data by iNIRS measurement. The intracranial data may include cerebral blood flow index data for one or more pulses of blood flow through blood vessels in the subject's brain tissue. The extracranial data may include blood pressure data for one or more pulses of blood flow through the subject's scalp vasculature. The control device 40 may be configured to process these two data streams acquired using the iNIRS system 10 and determine the ICP of the subject based on these two data streams. For example, the control device 40 may align the acquired scalp tissue blood pressure data with the acquired cerebral blood flow index data and be configured to determine an indication of the extracranial blood pressure value at which one or more blood vessels in the subject's brain tissue close from those data. Based on this critical closing pressure, the control device 40 may determine an indication of the ICP.

[0118] In the example described above with respect to FIGS. 2 to 4, the iNIRS system 10 uses one light source and one detector (i.e., there is only one light source-detector channel). However, this should not be considered limiting. The iNIRS system 10 may include a plurality of light sources and / or a plurality of photodetectors. Each light source may be coupled to a plurality of other detectors (e.g., via a plurality of reference channels). The plurality of photodetectors may be arranged (e.g., provided in the same region on the subject's scalp or very close to each other on the subject's scalp). And different photodetectors may be arranged to detect photons of sample light from the same light source that have been transmitted through similar regions of the subject's brain tissue, respectively. The control device 40 may be configured to combine data from different photodetectors (e.g., average the data to provide one combined measurement value for the subject's brain tissue). For example, the control device 40 may be configured to determine cerebral blood flow index data (and optionally also extracranial data) for the subject's brain tissue based on data acquired using a plurality of photodetectors. This arrangement may result in improved signal-to-noise for the measurements acquired using the iNIRS system 10.

[0119] The iNIRS system 10 may include a plurality of light source-detector channels related to a plurality of different regions of the subject's brain tissue. For example, a plurality of light detectors may be present at different locations on the subject's scalp (these light detectors may be coupled to the same light source or different light sources). The control device 40 may be configured to use the plurality of detectors of the iNIRS system 10 to obtain a plurality of ICP measurement values (as described above, but for each of the plurality of detectors). Then, the control device 40 may determine the ICP value of the subject based on the plurality of ICP measurement values from different detectors. With this arrangement, for example, since the ICP may be relatively constant in a plurality of different regions of the subject's brain tissue, the reliability of the measurement may be improved.

[0120] In the above example, the iNIRS system 10 may use one light source-detector channel to obtain both cerebral blood flow data and extracerebral blood flow data. However, the iNIRS system 10 need not obtain extracerebral blood flow data, and for example, an additional sensor may be provided to obtain an extracerebral blood pressure value. Further, or alternatively, different iNIRS light source-detector channels may be used to obtain extracerebral data, such as when the light source and the detector are arranged close to each other on the subject's scalp (e.g., to increase the options for photons of the sample light that travel a shorter distance from the light source to the detector). For example, the iNIRS system 10 may include an extracerebral light source-detector channel (one light source and one detector arranged to measure extracerebral blood flow), and one or more (e.g., a plurality of) light detectors arranged to measure cerebral blood flow.

[0121] In the foregoing example, extracranial blood flow data may be acquired using the iNIRS system 10 to measure the characteristics of blood flow in the subject's scalp tissue. However, this should not be considered limiting as other regions may be used for extracranial data. For example, the iNIRS system 10 may be configured to measure characteristics for the subject's neck, ear, forehead, etc. (e.g., when two or more light source-detector channels are used), or for regions further away from the subject's brain tissue. The iNIRS system 10 may be configured to acquire blood flow data for regions of the subject's body (not within the skull) when there are no significant external constraints on the blood flow being monitored (i.e., when the blood is transmitted through a region where it is not sufficiently compressed). For example, extracranial blood may flow through veins / arteries under the subject's skin in regions where it is not significantly compressed by surrounding substances.

[0122] The iNIRS system 10 may include a plurality of light sources. Those light sources may emit light in different wavelength ranges. The iNIRS system 10 may be configured to determine the ICP based on measurements obtained using light in each of a plurality of different wavelength ranges. The iNIRS system 10 may include a first light source configured to emit light in a wavelength range above the absorption wavelength for oxygen measurement, etc., and a second light source configured to emit light in a wavelength range below the absorption wavelength for oxygen measurement, etc. The control device 40 may be configured to determine the ICP based on the optical signals received from both the first light source and the second light source. Providing such a first light source and second light source may increase the reliability of the measurements when the value of blood oxygenation changes (e.g., because one of the light sources emits light in a wavelength range more suitable for absorption by oxygenated hemoglobin and the other light source emits light in a wavelength range more suitable for absorption by deoxygenated hemoglobin).

[0123] In the context of the present disclosure, it will be understood that the examples described herein are not intended to be limiting. On the contrary, specific potential ways of implementing the claimed technology are illustrated by way of example. For example, the iNIRS system 10 is described using a series of optical cables that provide a plurality of channels and a probe that couples those channels to the subject's scalp. However, it will be understood that the probe itself may be part of the optical channels or that no probe may be provided at all. Similarly, the placement of the reference channels is intended to indicate that the reference light is delivered from the light source to the photodetector via the optical channels (rather than through the subject's brain tissue). For example, each light source may comprise one reference channel for each photodetector, the reference channel directly connecting the light source to the photodetector. In that case, there may be no reference connections within the system at all. Alternatively, as shown in FIG. 1, the reference light may travel on a common reference optical channel, in which case a portion of the reference light is taken out from the common reference optical channel to each of the photodetectors. Also, the light sources may be arranged to deliver light to one of a plurality of different locations on the subject's scalp. For example, the light sources may each be coupled to a plurality of different sample delivery channels that extend towards the subject's scalp (e.g., from an optical splitter).

[0124] It will be understood that it is not necessary to consider the particular arrangement shown for the signal processing circuit of the detector to be limiting. Each optical detection device 130 combines sample light and reference light to provide a combined optical signal having components of one or more beat frequencies, and processes the combined optical signal to determine one or more characteristics of the subject's brain tissue. For this purpose, any suitable signal processing circuit and / or conversion circuit may also be used. For example, a transimpedance amplifier may not be necessary (e.g., depending on the photodetector / ADC, current-voltage conversion may not be necessary, or current-voltage conversion may be performed in a different manner). Similarly, a balanced photodetector need not be used, and instead a single photodetector such as a photodiode may be used. Similarly, the arrangement with ADCs shown in multiple figures need not be considered limiting. For example, a number of ADCs (e.g., one for each detector output stream) may be used, or the output streams of all detectors may be supplied to a single common ADC.

[0125] Furthermore, as understood in the context of the present disclosure, the foregoing teachings are realizable using time-domain diffuse correlation spectroscopy (TD-DCS system). For example, one aspect of the present disclosure may provide a TD-DCS system configured to obtain an indication of such a pulsatile waveform of cerebral blood flow, and the control device 40 may be configured to process this TD-DCS data to obtain an indication of ICP.

[0126] From the above considerations, it will be understood that the examples shown in the plurality of figures are merely illustrative and may include features that can be generalized, removed, or replaced as described in this specification and recited in the claims. Referring to the drawings, generally, it will be understood that schematic functional block diagrams are used to illustrate the functions of the systems and apparatuses described in this specification. Additionally, the processing functions may also be provided by apparatuses supported by electronic devices. However, it will be understood that the functions need not be divided in this way and should not be construed as suggesting a particular structure of hardware other than those described and claimed below. One or more of the functions of the elements shown in the drawings may be further subdivided and / or distributed throughout the apparatuses of the present disclosure. In some examples, the functions of one or more of the elements shown in the drawings may be integrated into one functional unit.

[0127] As will be understood by those skilled in the art in the context of the present disclosure, each of the examples described in this specification may be implemented in a variety of different ways. The features of the aspects of the present disclosure may be combined with any of the other aspects of the present disclosure. For example, an aspect of a method may be combined with an aspect of an apparatus, and features described with reference to the operation of a particular element of an apparatus may be provided in a method that does not use that particular type of apparatus. Additionally, the features of each example are intended to be separable from the features described together, unless explicitly stated that some other features are essential for its operation. Each of these separable features may, of course, be combined with any of the other features of the example in which the feature is described, or with any of the other features, or with any combination of the features of any other example described in this specification. Furthermore, equivalents and modifications not mentioned above may also be employed without departing from the present invention.

[0128] Certain features of the methods described herein may be implemented in hardware, and one or more functions of the apparatus may be implemented in the steps of the method. Also, in the context of the present disclosure, it will be understood that the methods described herein need not be performed in the order described, nor necessarily in the order depicted in the drawings. Thus, aspects of the present disclosure described with reference to a product or apparatus are also intended to be implemented as a method, and vice versa. The methods described herein may be implemented in a computer program, in hardware, or in any combination thereof. A computer program includes software, middleware, firmware, or any combination thereof. Such a program may be provided as a signal or network message, or may be recorded on a computer-readable medium such as a tangible computer-readable medium capable of storing the computer program in a non-transitory form. Hardware includes a computer, a portable device, a programmable processor, a general-purpose processor, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a logic gate array, and the like.

[0129] Any control device of the present disclosure may be implemented using fixed logic such as an assembly of logic gates, or programmable logic such as software and / or instructions of a computer program executed by a processor. The control device may include a central processing unit (CPU) and its associated memory, which are connected to an image processing unit (GPU) and its associated memory. Other types of programmable logic include programmable processors, programmable digital logic (e.g., field programmable gate arrays (FPGAs)), tensor processing units (TPUs), erasable programmable read-only memories (EPROMs), electrically erasable programmable read-only memories (EEPROMs), application specific integrated circuits (ASICs), or other types of digital logic, software, code, electronic instructions, flash memory, optical disks, CD-ROMs, DVD ROMs, magnetic cards or optical cards, other types of machine-readable media suitable for storing electronic instructions, or any suitable combination thereof. In particular, any control device of the present disclosure may be provided by an ASIC.

[0130] Other examples and variations of the present disclosure will be apparent to those skilled in the art in the context of the present disclosure.

Claims

1. A light source configured to emit light, A sample delivery channel is coupled to the light source and arranged to be coupled to the subject's scalp in order to deliver light from the light source toward the subject's brain tissue, A reference channel coupled to the light source in order to receive light from the light source, A light-emitting device equipped with, A photodetector configured such that the scalp of the subject and the light-emitting device are coupled, the photodetector comprising an interferometric photodetector configured to receive (i) reference light from the reference channel and (ii) sample light from the subject's brain, which includes light emitted from the light source, A non-invasive intracranial pressure detection device comprising an interferometric near-infrared spectroscopy (iNIRS) system, The interference photodetector is arranged to couple the sample light and the reference light in order to provide a coupled optical signal that includes one or more components of the beat frequency between the sample light and the reference light. The aforementioned light detection device is A control device configured to process data indicating the coupled optical signal in order to determine the intracranial pressure of the subject by acquiring cerebral blood flow data based on at least one characteristic of the pulsation waveform of one or more identified pulses of blood flow through the subject's brain, and extracerebral blood flow data indicating one or more of the pulses of blood flow through an extracerebral region of the subject's body. Equipped with, A non-invasive intracranial pressure detection device characterized by the following features.

2. The extracerebral blood flow data mentioned above is, The blood pressure indication of the pulse of blood flow passing through the extracerebral region of the subject's body, including, The non-invasive intracranial pressure detection device according to claim 1.

3. The control device is configured to determine the instruction for the intracranial pressure of the subject based on (i) the pulsating waveform of one or more identified pulses of blood flow through the subject's brain, and (ii) the corresponding pulsating waveform of one or more pulses of blood flow through the extracranial region of the subject's body for the blood pressure. The non-invasive intracranial pressure detection device according to claim 2.

4. The control device is configured to determine the instruction for the intracranial pressure of the subject based on the identified critical closure pressure of the blood vessels in the subject's brain. The non-invasive intracranial pressure detection device according to claim 3.

5. The control device is configured to process the data indicating the coupled optical signals in order to acquire cerebral blood flow index data of blood flow through the subject's brain, The pulsating waveform of one or more identified pulses of blood flow through the brain of the subject is The pulsating waveform of the aforementioned cerebral blood flow indicator, including, A non-invasive intracranial pressure detection device according to any one of claims 1 to 4.

6. The light detection device is configured to acquire the extracerebral blood flow data using the iNIRS system, The iNIRS system is optionally configured to acquire both the extracerebral blood flow data and the cerebral blood flow data using the same light source / detector channel. The non-invasive intracranial pressure detection device according to claim 1.

7. The iNIRS system is configured to acquire extracerebral blood flow index data. The control device is configured to process the extracerebral blood flow index data in order to obtain the value of extracerebral blood pressure. The non-invasive intracranial pressure detection device according to claim 6.

8. The photodetector is configured to be coupled to the scalp of the subject so that the detector acquires a coupled optical signal that includes both (i) a beat frequency component related to the sample light transmitted from the subject's brain and (ii) a beat frequency component related to the sample light transmitted from the extrabrain region of the subject's body. The non-invasive intracranial pressure detection device according to claim 6 or 7.

9. The control device is configured to separate data related to the subject's brain from data related to the extra-brain regions of the subject's body. The non-invasive intracranial pressure detection device according to claim 8.

10. The control device is configured to separate the data based on the time of flight of the sample light. The non-invasive intracranial pressure detection device according to claim 9.

11. The iNIRS system is Multiple photodetectors, Equipped with, Each of the aforementioned photodetectors is configured to acquire cerebral blood flow data from the subject's brain. The non-invasive intracranial pressure detection device according to claim 1.

12. The control device is configured to determine the intracranial pressure based on the characteristics of the pulsating waveform of the blood flow pulses passing through the subject's brain, as detected by the plurality of photodetectors. The non-invasive intracranial pressure detection device according to claim 11.

13. The apparatus is configured to acquire extracerebral blood flow data from different extracerebral regions of the subject's body based on coupled optical signals associated with different detectors. A non-invasive intracranial pressure detection device according to claim 11 or 12.

14. The light source is configured to emit wavelength-swept light. The iNIRS system according to claim 1.

15. The iNIRS system is (i) an intracerebral light source-detector channel configured to acquire cerebral blood flow data, and (ii) an extracerebral light source-detector channel configured to acquire extracerebral blood flow data, Equipped with, The non-invasive intracranial pressure detection device according to claim 1.

16. The aforementioned light detection device is An extracerebral blood flow sensor configured to acquire extracerebral blood flow data, Equipped with, The extracerebral blood flow sensor is optionally configured to acquire the pressure value of the pulse of extracerebral blood flow. The non-invasive intracranial pressure detection device according to claim 1.

17. The control device is configured to determine the intracranial pressure based on the difference between the diastolic and systolic values ​​of one or more pulses of blood flow through the subject's brain, The control device is optionally configured to determine the instruction based on the pulse coefficient of the blood flow through the subject's brain. The non-invasive intracranial pressure detection device according to claim 1.

18. The iNIRS system is Two or more light sources, Equipped with, The first light source is configured to emit wavelength-swept light passing through a plurality of wavelengths above the isoabsorptural wavelength of oxygen measurement, The second light source is configured to emit wavelength-swept light passing through a plurality of wavelengths below the isoabsorptural wavelength of the oxygen measurement, The control device is configured to determine the instruction for the intracranial pressure based on the sample light received from each of the two light sources. The non-invasive intracranial pressure detection device according to claim 1.

19. The control device is configured to acquire time-of-flight data based on the coupled optical signals, The aforementioned flight time data is, A data surface including the time-ordered distribution of the time-of-flight sequence of photons of sample light from the light source reaching the photodetector, including, The non-invasive intracranial pressure detection device according to claim 1.

20. The control device is configured to obtain cerebral blood flow data based on changes in the data surface, The control device is optionally configured to determine the cerebral blood flow data based on the attenuation rate associated with the data surface. The non-invasive intracranial pressure detection device according to claim 19.

21. The control device is configured to acquire instructions for one or more optical properties of the subject's brain based on the time-of-flight data, One or more of the optical properties of the subject's brain are, at the discretion of the subject, Scattering coefficient and / or absorption coefficient, Includes, The control device is configured to obtain cerebral blood flow data of the subject's brain based on one or more of the optical properties of the subject's brain. The non-invasive intracranial pressure detection device according to claim 20.

22. A non-invasive method for detecting intracranial pressure, The process of operating a light source to emit light, The process of delivering (i) light from the light source to the subject's brain through a sample channel and (ii) light through a reference channel, In an interferometric photodetector, the process includes receiving (i) reference light from the reference channel and (ii) sample light from the subject's brain, which includes light emitted from the light source. In the aforementioned interferometric photodetector, in order to provide a coupled optical signal that includes one or more components of the beat frequency between the sample light and the reference light, the steps include coupling the sample light and the reference light, A step of processing data representing the coupled optical signal in order to determine the intracranial pressure of the subject by obtaining cerebral blood flow data based on at least one characteristic of the pulsation waveform of one or more identified pulses of blood flow through the subject's brain, and extracerebral blood flow data representing one or more of the pulses of blood flow through an extracerebral region of the subject's body, including, A non-invasive method for detecting intracranial pressure, characterized by the following features.

23. Computer program instructions configured to program a control device in order to control the operation of a light-emitting device and a light-detecting device and perform the method according to claim 22, Having, A computer program product characterized by the following features.

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